Apparatus for destroying dividing cells

ABSTRACT

An apparatus is provided for selectively destroying dividing cells in living tissue formed of dividing cells and non-dividing cells. The dividing cells contain polarizable intracellular members and during late anaphase or telophase, the dividing cells are connected to one another by a cleavage furrow. The apparatus includes a generator and insulated electrodes for subjecting the living tissue to electric field conditions sufficient to cause movement of the polarizable intracellular members toward the cleavage furrow in response to a non-homogeneous electric field being induced in the dividing cells. The non-homogeneous electric field produces an increased density electric field in the region of the cleavage furrow. The movement of the polarizable intracellular intracellular members towards the cleavage furrow causes the breakdown thereof which results in the destruction of the dividing cells, while the non-dividing cells of the living tissue remain intact.

TECHNICAL FIELD

[0001] This invention concerns selective destruction of rapidly dividingcells, and more particularly, to an apparatus for selectively destroyingdividing cells by applying an electric field having certain prescribedcharacteristics.

BACKGROUND

[0002] All living organisms proliferate by cell division, including cellcultures, microorganisms (such as bacteria, mycoplasma, yeast, protozoa,and other single-celled organisms), fungi, algae, plant cells, etc.Dividing cells of organisms can be destroyed, or their proliferationcontrolled, by methods that are based on the sensitivity of the dividingcells of these organisms to certain agents. For example, certainantibiotics stop the multiplication process of bacteria.

[0003] The process of eukaryotic cell division is called “mitosis”,which involves nice distinct phases (see Darnell et al., Molecular CellBiology, New York: Scientific American Books, 1986, p. 149). Duringinterphase, the cell replicates chromosomal DNA, which begins condensingin early prophase. At this point, centrioles (each cell contains 2)begin moving towards opposite poles of the cell. In middle prophase,each chromosome is composed of duplicate chromatids. Microtubularspindles radiate from regions adjacent to the centrioles, which arecloser to their poles. By late prophase, the centrioles have reached thepoles, and some spindle fibers extend to the center of the cell, whileothers extend from the poles to the chromatids. The cells then move intometaphase, when the chromosomes move toward the equator of the cell andalign in the equatorial plane. Next is early anaphase, during which timedaughter chromatids separate from each other at the equator by movingalong the spindle fibers toward a centromere at opposite poles. The cellbegins to elongate along the axis of the pole; the pole-to-pole spindlesalso elongate. Late anaphase occurs when the daughter chromosomes (asthey are not called) each reach their respective opposite poles. At thispoint, cytokinesis begins as the cleavage furrow begins to form at theequator of the cell. In other words, late anaphase is the point at whichpinching the cell membrane begins. During telophase, cytokinesis isnearly complete and spindles disappear. Only a relatively narrowmembrane connection joins the two cytoplasms. Finally, the membranesseparate fully, cytokinesis is complete and the cell returns tointerphase.

[0004] In meisosis, the cell undergoes a second division, involvingseparation of sister chromosomes to opposite poles of the cell alongspindle fibers, followed by formation of a cleavage furrow and celldivision. However, this division is not preceded by chromosomereplication, yielding a haploid germ cell.

[0005] Bacteria also divide by chromosome replication, followed by cellseparation. However, since the daughter chromosomes separate byattachment to membrane components; there is no visible apparatus thatcontributes to cell division as in eukaryotic cells.

[0006] It is well known that tumors, particularly malignant or canceroustumors, grow uncontrollably compared to normal tissue. Such expeditedgrowth enables tumors to occupy an ever-increasing space and to damageor destroy tissue adjacent thereto. Furthermore, certain cancers arecharacterized by an ability to transmit cancerous “seeds”, includingsingle cells or small cell clusters (metastasises), to new locationswhere the messastatic cancer cells grow into additional tumors.

[0007] The rapid growth of tumors, in general, and malignant tumors inparticular, as described above, is the result of relatively frequentcell division or multiplication of these cells compared to normal tissuecells. The distinguishably frequent cell division of cancer cells is thebasis for the effectiveness of existing cancer treatments, e.g.,irradiation therapy and the use of various chemo-therapeutic agents.Such treatments are based on the fact that cells undergoing division aremore sensitive to radiation and chemo-therapeutic agents thannon-dividing cells. Because tumors cells divide much more frequentlythan normal cells, it is possible, to a certain extent, to selectivelydamage or destroy tumor cells by radiation therapy and/or chemotherapy.The actual sensitivity of cells to radiation, therapeutic agents, etc.,is also dependent on specific characteristics of different types ofnormal or malignant cell types. Thus, unfortunately, the sensitivity oftumor cells is not sufficiently higher than that many types of normaltissues. This diminishes the ability to distinguish between tumor cellsand normal cells, and therefore, existing cancer treatments typicallycause significant damage to normal tissues, thus limiting thetherapeutic effectiveness of such treatments. Furthermore, theinevitable damage to other tissue renders treatments very traumatic tothe patients and, often, patients are unable to recover from a seeminglysuccessful treatment. Also, certain types of tumors are not sensitive atall to existing methods of treatment.

[0008] There are also other methods for destroying cells that do notrely on radiation therapy or chemotherapy alone. For example, ultrasonicand electrical methods for destroying tumor cells can be used inaddition to or instead of conventional treatments. Electric fields andcurrents have been used for medical purposes for many years. The mostcommon is the generation of electric currents in a human or animal bodyby application of an electric field by means of a pair of conductiveelectrodes between which a potential difference is maintained. Theseelectric currents are used either to exert their specific effects, i.e.,to stimulate excitable tissue, or to generate heat by flowing in thebody since it acts as a resistor. Examples of the first type ofapplication include the following: cardiac defibrillators, peripheralnerve and muscle stimulators, brain stimulators, etc. Currents are usedfor heating, for example, in devices for tumor ablation, ablation ofmalfunctioning cardiac or brain tissue, cauterization, relaxation ofmuscle rheumatic pain and other pain, etc.

[0009] Another use of electric fields for medical purposes involves theutilization of high frequency oscillating fields transmitted from asource that emits an electric wave, such as an RF wave or a microwavesource that is directed at the part of the body that is of interest(i.e., target). In these instances, there is no electric energyconduction between the source and the body; but rather, the energy istransmitted to the body by radiation or induction. More specifically,the electric energy generated by the source reaches the vicinity of thebody via a conductor and is transmitted from it through air or someother electric insulating material to the human body.

[0010] In a conventional electrical method, electrical current isdelivered to a region of the target tissue using electrodes that areplaced in contact with the body of the patient. The applied electricalcurrent destroys substantially all cells in the vicinity of the targettissue. Thus, this type of electrical method does not discriminatebetween different types of cells within the target tissue and results inthe destruction of both tumor cells and normal cells.

[0011] Electric fields that can be used in medical applications can thusbe separated generally into two different modes. In the first mode, theelectric fields are applied to the body or tissues by means ofconducting electrodes. These electric fields can be separated into twotypes, namely (1) steady fields or fields that change at relatively slowrates, and alternating fields of low frequencies that inducecorresponding electric currents in the body or tissues, and (2) highfrequency alternating fields (above 1 MHz) applied to the body by meansof the conducting electrodes. In the second mode, the electric fieldsare high frequency alternating fields applied to the body by means ofinsulated electrodes.

[0012] The first type of electric field is used, for example, tostimulate nerves and muscles, pace the heart, etc. In fact, such fieldsare used in nature to propagate signals in nerve and muscle fibers,central nervous system (CNS), heart, etc. The recording of such naturalfields is the basis for the ECG, EEG, EMG, ERG, etc. The field strengthin these applications, assuming a medium of homogenous electricproperties, is simply the voltage applied to the stimulating/recordingelectrodes divided by the distance between them. These currents can becalculated by Ohm's law and can have dangerous stimulatory effects onthe heart and CNS and can result in potentially harmful ionconcentration changes. Also, if the currents are strong enough, they cancause excessive heating in the tissues. This heating can be calculatedby the power dissipated in the tissue (the product of the voltage andthe current).

[0013] When such electric fields and currents are alternating, theirstimulatory power, on nerve, muscle, etc., is an inverse function of thefrequency. At frequencies above 1-10 KHz, the stimulation power of thefields approaches zero. This limitation is due to the fact thatexcitation induced by electric stimulation is normally mediated bymembrane potential changes, the rate of which is limited by the RCproperties (time constants on the order of 1 ms) of the membrane.

[0014] Regardless of the frequency, when such current inducing fieldsare applied, they are associated with harmful side effects caused bycurrents. For example, one negative effect is the changes in ionicconcentration in the various “compartments” within the system, and theharmful products of the electrolysis taking place at the electrodes, orthe medium in which the tissues are imbedded. The changes in ionconcentrations occur whenever the system includes two or morecompartments between which the organism maintains ion concentrationdifferences. For example, for most tissues, [Ca⁺⁺] in the extracellularfluid is about 2×10⁻³ M, while in the cytoplasm of typical cells itsconcentration can be as low as 10⁻⁷ M. A current induced in such asystem by a pair of electrodes, flows in part from the extracellularfluid into the cells and out again into the extracellular medium. About2% of the current flowing into the cells is carried by the Ca⁺⁺ ions. Incontrast, because the concentration of intracellular Ca⁺⁺ is muchsmaller, only a negligible fraction of the currents that exits the cellsis carried by these ions. Thus, Ca⁺⁺ ions accumulate in the cells suchthat their concentrations in the cells increases, while theconcentration in the extracellular compartment may decrease. Theseeffects are observed for both DC and alternating currents (AC). The rateof accumulation of the ions depends on the current intensity ionmobilities, membrane ion conductance, etc. An increase in [Ca⁺⁺] isharmful to most cells and if sufficiently high will lead to thedestruction of the cells. Similar considerations apply to other ions. Inview of the above observations, long term current application to livingorganisms or tissues can result in significant damage. Another majorproblem that is associated with such electric fields, is due to theelectrolysis process that takes place at the electrode surfaces. Herecharges are transferred between the metal (electrons) and theelectrolytic solution (ions) such that charged active radicals areformed. These can cause significant damage to organic molecules,especially macromolecules and thus damage the living cells and tissues.

[0015] In contrast, when high frequency electric fields, above 1 MHz andusually in practice in the range of GHz, are induced in tissues usuallyby means of insulated electrodes or transmission of e.m. waves, thesituation is quite different. These type of fields generate onlycapacitive or displacement currents, rather than the conventional chargeconducting currents. Under the effect of this type of field, livingtissues behave mostly according to their dielectric properties ratherthan their electric conductive properties. Therefore, the dominant fieldeffect is that due to dielectric losses and heating. Thus, it is widelyaccepted that in practice, the meaningful effects of such fields onliving organisms, are only those due to their heating effects, i.e., dueto dielectric losses.

[0016] In U.S. Pat. No. 6,043,066 ('066) to Mangano, a method and deviceare presented which enable discrete objects having a conducting innercore, surrounded by a dielectric membrane to be selectively inactivatedby electric fields via irreversible breakdown of their dielectricmembrane. One potential application for this is in the selection andpurging of certain biological cells in a suspension. According to the'066 patent, an electric field is applied for targeting selected cellsto cause breakdown of the dielectric membranes of these tumor cells,while purportedly not adversely affecting other desired subpopulationsof cells. The cells are selected on the basis of intrinsic or induceddifferences in a characteristic electroporation threshold. Thedifferences in this threshold can depend upon a number of parameters,including the difference in cell size.

[0017] The method of the '066 patent is therefore based on theassumption that the electroporation threshold of tumor cells issufficiently distinguishable from that of normal cells because ofdifferences in cell size and differences in the dielectric properties ofthe cell membranes. Based upon this assumption, the larger size of manytypes of tumor cells makes these cells more susceptible toelectroporation and thus, it may be possible to selectively damage onlythe larger tumor cell membranes by applying an appropriate electricfield. One disadvantage of this method is that the ability todiscriminate is highly dependent upon cell type, for example, the sizedifference between normal cells and tumor cells is significant only incertain types of cells. Another drawback of this method is that thevoltages which are applied can damage some of the normal cells and maynot damage all of the tumor cells because the differences in size andmembrane dielectric properties are largely statistical and the actualcell geometries and dielectric properties can vary significantly.

[0018] What is needed in the art and has heretofore not been availableis an apparatus for killing dividing cells, wherein the apparatus betterdiscriminates between dividing cells, including single-celled organisms,and non-dividing cells and is capable of selectively destroying thedividing cells or organisms with substantially no affect on thenon-dividing cells or organisms.

SUMMARY

[0019] An apparatus for use in a number of different applications forselectively destroying cells undergoing growth and division is provided.This includes, cell, particularly tumor cells, in living tissue andsingle-celled organisms. The apparatus can be incorporated into a numberof different configurations (e.g., as a skin patch or embeddedinternally within the body) to eliminate or control the growth of suchliving tissue or organisms.

[0020] A major use of the present apparatus is in the treatment oftumors by selective destruction of tumor cells with substantially noaffect on normal tissue cells, and thus, the exemplary apparatus isdescribed below in the context of selective destruction of tumor cells.It should be appreciated however, that for purpose of the followingdescription, the term “cell” may also refer to a single-celled organism(eubacteria, bacteria, yeast, protozoa), multi-celled organisms (fungi,algae, mold), and plants as or parts thereof that are not normallyclassified as “cells”. The exemplary apparatus enables selectivedestruction of cells undergoing division in a way that is more effectiveand more accurate (e.g., more adaptable to be aimed at specific targets)than existing methods. Further, the present apparatus causes minimaldamage, if any, to normal tissue and, thus, reduces or eliminates manyside-effects associated with existing selective destruction methods,such as radiation therapy and chemotherapy. The selective destruction ofdividing cells using the present apparatus does not depend on thesensitivity of the cells to chemical agents or radiation. Instead, theselective destruction of dividing cells is based on distinguishablegeometrical and structural characteristics of cells undergoing division,in comparison to non-dividing cells, regardless of the cell geometry ofthe type of cells being treated.

[0021] According to one exemplary embodiment, cell geometry-dependentselective destruction of living tissue is performed by inducing anon-homogenous electric field in the cells using an electronicapparatus.

[0022] It has been observed by the present inventor that, whiledifferent cells in their non-dividing state may have different shapes,e.g., spherical, ellipsoidal, cylindrical, “pancake-like”, etc., thedivision process of practically all cells is characterized bydevelopment of a “cleavage furrow” in late anaphase and telophase. Thiscleavage furrow is a slow constriction of the cell membrane (between thetwo sets of daughter chromosomes) which appears microscopically as agrowing cleft (e.g., a groove or notch) that gradually separates thecell into two new cells. During the division process, there is atransient period (telophase) during which the cell structure isbasically that of two sub-cells interconnected by a narrow “bridge”formed of the cell material. The division process is completed when the“bridge” between the two sub-cells is broken. The selective destructionof tumor cells using the present electronic apparatus utilizes thisunique geometrical feature of dividing cells.

[0023] When a cell or a group of cells are under natural conditions orenvironment, i.e., part of a living tissue, they are disposed surroundedby a conductive environment consisting mostly of an electrolyticinter-cellular fluid and other cells that are composed mostly of anelectrolytic intra-cellular liquid. When an electric field is induced inthe living tissue, by applying an electric potential across the tissue,an electric field is formed in the tissue and the specific distributionand configuration of the electric field lines defines the paths ofelectric currents in the tissue, if currents are in fact induced in thetissue. The distribution and configuration of the electric field isdependent on various parameters of the tissue, including the geometryand the electric properties of the different tissue components, and therelative conductivities, capacities and dielectric constants (that maybe frequency dependent) of the tissue components.

[0024] The electric current flow pattern for cells undergoing divisionis very different and unique as compared to non-dividing cells. Suchcells including first and second sub-cells, namely an “original” celland a newly formed cell, that are connected by a cytoplasm “bridge” or“neck”. The currents penetrate the first sub-cell through part of themembrane (“the current source pole”); however, they do not exit thefirst sub-cell through a portion of its membrane closer to the oppositepole (“the current sink pole”). Instead, the lines of current flowconverge at the neck or cytoplasm bridge, whereby the density of thecurrent flow lines is greatly increased. A corresponding, “mirrorimage”, process that takes place in the second sub-cell, whereby thecurrent flow lines diverge to a lower density configuration as theydepart from the bridge, and finally exit the second sub-cell from a partof its membrane closes to the current sink.

[0025] When a polar or a polarizable object is placed in a non-uniformconverging or diverging field, electric forces act on it and pull ittowards the higher density electric field lines. In the case of dividingcell, electric forces are exerted in the direction of the cytoplasmbridge between the two cells. Since all intercellular organelles arepolarizable, and most macromolecules are polar (have a dipole moment)they are all force towards the bridge between the two cells. The fieldpolarity is irrelevant to the direction of the force and, therefore, analternating electric having specific properties can be used to producesubstantially the same effect. It will also be appreciated that theconcentrated electric field present in or near the bridge or neckportion in itself exerts strong forces on charges and natural dipolesand can lead to the disruption of structures associated with thesemembers.

[0026] The movement of the cellular organelles towards the bridgedisrupts the cell structure and results in increased pressure in thevicinity of the connecting bridge membrane. This pressure of theorganelles on the bridge membrane is expected to break the bridgemembrane and, thus, it is expected that the dividing cell will “explode”in response to this pressure. The ability to break the membrane anddisrupt other cell structures can be enhanced by applying a pulsatingalternating electric field that has a frequency from about 50 KHz toabout 500 KHz. When this type of electric field is applied to thetissue, the forces exerted on the intercellular organelles have a“hammering” effect, whereby force pulses (or beats) are applied to theorganelles numerous times per second, enhancing the movement oforganelles of different sizes and masses towards the bridge (or neck)portion from both of the sub-cells, thereby increasing the probabilityof breaking the cell membrane at the bridge portion. The forces exertedon the intracellular organelles also affect the organelles themselvesand may collapse or break the organelles.

[0027] According to one exemplary embodiment, the apparatus for applyingthe electric field is an electronic apparatus that generates the desiredelectric signals in the shape of waveforms or trains of pulses. Theelectronic apparatus includes a generator that generates an alternatingvoltage waveform at frequencies in the range from about 50 KHz to about500 KHz. The generator is operatively connected to conductive leadswhich are connected at their other ends to insulatedconductors/electrodes (also referred to as isolects) that are activatedby the generated waveforms. The insulated electrodes consist of aconductor in contact with a dielectric (insulating layer) that is incontact with the conductive tissue, thus forming a capacitor. Theelectric fields that are generated by the present apparatus can beapplied in several different modes depending upon the precise treatmentapplication.

[0028] In one exemplary embodiment, the electric fields are applied byexternal insulated electrodes which are constructed so that the appliedelectric fields can be of a local type or of a widely distributed type.This embodiment is designed to treat skin tumors and lesions that areclose to the skin surface. According to this embodiment, the insulatedelectrodes can be incorporated into a skin patch that is applied to askin surface. The skin patch can be a self-adhesive flexible patch andcan include one or more pairs of the insulated electrodes.

[0029] According to another embodiment, the apparatus is used in aninternal type application in that the insulated electrodes are in theform of plates, wires, etc., that are inserted subcutaneously or deeperwithin the body so as to generate an electric field having the abovedesired properties at a target area (e.g., a tumor).

[0030] Thus, the present apparatus utilizes electric fields that fallinto a special intermediate category relative to previous high and lowfrequency applications in that the present electric fields arebio-effective fields that have no meaningful stimulatory effects and nothermal effects. Advantageously, when non-dividing cells are subjectedto these electric fields, there is no effect on the cells; however, thesituation is much different when dividing cells are subjected to thepresent electric fields. Thus, the present electronic apparatus and thegenerated electric fields target dividing cells, such as tumors or thelike, and do not target non-dividing cells that is found around inhealthy tissue surrounding the target area. Furthermore, since thepresent apparatus utilizes insulated electrodes, the above mentionednegative effects, obtained when conductive electrodes are used, i.e.,ion concentration changes in the cells and the formation of harmfulagents by electrolysis, do not occur with the present apparatus. This isbecause, in general, no actual transfer of charges takes place betweenthe electrodes and the medium, and there is no charge flow in the mediumwhere the currents are capacitive.

[0031] It should be appreciated that the present electronic apparatuscan also be used in applications other than treatment of tumors in theliving body. In fact, the selective destruction utilizing the presentapparatus can be used in conjunction with any organism that proliferatesdivision and multiplication, for example, tissue cultures,microorganisms, such as bacteria, mycoplasma, protozoa, fungi, algae,plant cells, etc. Such organisms divide by the formation of a groove orcleft as described above. As the groove or cleft deepens, a narrowbridge is formed between the two parts of the organism, similar to thebridge formed between the sub-cells of dividing animal cells. Since suchorganisms are covered by a membrane having a relatively low electricconductivity, similar to an animal cell membrane described above, theelectric field lines in a dividing organism converge at the bridgeconnecting the two parts of the dividing organism. The converging fieldlines result in electric forces that displace polarizable elementswithin the dividing organism.

[0032] The above, and other objects, features and advantages of thepresent apparatus will become apparent from the following descriptionread in conjunction with the accompanying drawings, in which likereference numerals designate the same elements.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

[0033] FIGS. 1A-1E are simplified, schematic, cross-sectional,illustrations of various stages of a cell division process;

[0034]FIGS. 2A and 2B are schematic illustrations of a non-dividing cellbeing subjected to an electric field;

[0035]FIGS. 3A, 3B and 3C are schematic illustrations of a dividing cellbeing subjected to an electric field according to one exemplaryembodiment, resulting in destruction of the cell (FIG. 3C) in accordancewith one exemplary embodiment;

[0036]FIG. 4 is a schematic illustration of a dividing cell at one stagebeing subject to an electric field;

[0037]FIG. 5 is a schematic diagram of an apparatus for applying anelectric according to one exemplary embodiment for selectivelydestroying cells;

[0038]FIG. 6 is a simplified schematic diagram of an equivalent electriccircuit of insulated electrodes of the apparatus of FIG. 5;

[0039]FIG. 7 is a schematic illustration of a skin patch incorporatingthe apparatus of FIG. 5 and for placement on a skin surface for treatinga tumor or the like;

[0040]FIG. 8 is a schematic illustration of the insulated electrodesimplanted within the body for treating a tumor or the like;

[0041]FIG. 9 is a schematic illustration of the insulated electrodesimplanted within the body for treating a tumor or the like;

[0042] FIGS. 10A-10D are schematic illustrations of variousconstructions of the insulated electrodes of the apparatus of FIG. 5;

[0043]FIG. 11 is a schematic illustration of two insulated electrodesbeing arranged about a human torso for treatment of a tumor containerwithin the body, e.g., a tumor associated with lung cancer;

[0044] FIGS. 12A-12C are schematic illustrations of various insulatedelectrodes with and without protective members formed as a part of theconstruction thereof; and

[0045]FIG. 13 is a schematic illustration of insulated electrodes thatare arranged for focusing the electric field at a desired target whileleaving other areas in low field density (i.e., protected areas).

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0046] Reference is made to FIGS. 1A-1E which schematically illustratevarious stages of a cell division process. FIG. 1A illustrates a cell 10at its normal geometry, which can be generally spherical (as illustratedin the drawings), ellipsoidal, cylindrical, “pancake-like” or any othercell geometry, as is known in the art. FIGS. 1B-1D illustrate cell 10during different stages of its division process, which results in theformation of two new cells 18 and 20, shown in FIG. 1E.

[0047] As shown in FIGS. 1B-1D, the division process of cell 10 ischaracterized by a slowly growing cleft 12 which gradually separatescell 10 into two units, namely sub-cells 14 and 16, which eventuallyevolve into new cells 18 and 20 (FIG. 1E). A shown specifically in FIG.1D, the division process is characterized by a transient period duringwhich the structure of cell 10 is basically that of the two sub-cells 14and 16 interconnected by a narrow “bridge” 22 containing cell material(cytoplasm surrounded by cell membrane).

[0048] Reference is now made to FIGS. 2A and 2B, which schematicallyillustrate non-dividing cell 10 being subjected to an electric fieldproduced by applying an alternating electric potential, at a relativelylow frequency and at a relatively high frequency, respectively. Cell 10includes intracellular organelles, e.g., a nucleus 30. Alternatingelectric potential is applied across electrodes 28 and 32 that can beattached externally to a patient at a predetermined region, e.g., in thevicinity of the tumor being treated. When cell 10 is under naturalconditions, i.e., part of a living tissue, it is disposed in aconductive environment (hereinafter referred to as a “volume conductor”)consisting mostly of electrolytic inter-cellular liquid. When anelectric potential is applied across electrodes 28 and 32, some of thefield lines of the resultant electric field (or the current induced inthe tissue in response to the electric field) penetrate the cell 10,while the rest of the field lines (or induced current) flow in thesurrounding medium. The specific distribution of the electric fieldlines, which is substantially consistent with the direction of currentflow in this instance, depends on the geometry and the electricproperties of the system components, e.g., the relative conductivitiesand dielectric constants of the system components, that can be frequencydependent. For low frequencies, e.g., frequencies lower than 10 KHz, theconductance properties of the components completely dominate the currentflow and the field distribution, and the field distribution is generallyas depicted in FIG. 2A. At higher frequencies, e.g., at frequencies ofbetween 10 KHz and 1 MHz, the dielectric properties of the componentsbecomes more significant and eventually dominate the field distribution,resulting in field distribution lines as depicted generally in FIG. 2B.

[0049] For constant (i.e., DC) electric fields or relatively lowfrequency alternating electric fields, for example, frequencies under 10KHz, the dielectric properties of the various components are notsignificant in determining and computing the field distribution.Therefore, as a first approximation, with regard to the electric fielddistribution, the system can be reasonably represented by the relativeimpedances of its various components. Using this approximation, theintercellular (i.e., extracellular) fluid and the intracellular fluideach has a relatively low impedance, while the cell membrane 11 has arelatively high impedance. Thus, under low frequency conditions, only afraction of the electric field lines (or currents induced by theelectric field) penetrate membrane 11 of the cell 10. At relatively highfrequencies (e.g., 10 KHz-1 MHz), in contrast, the impedance of membrane11 relative to the intercellular and intracellular fluids decreases, andthus, the fraction of currents penetrating the cells increasessignificantly. It should be noted that at very high frequencies, i.e.,above 1 MHz, the membrane capacitance can short the membrane resistanceand, therefore, the total membrane resistance can become negligible.

[0050] In any of the embodiments described above, the electric fieldlines (or induced currents) penetrate cell 10 from a portion of themembrane 11 closest to one of the electrodes generating the current,e.g., closest to positive electrode 28 (also referred to herein as“source”). The current flow pattern across cell 10 is generally uniformbecause, under the above approximation, the field induced inside thecell is substantially homogeneous. The currents exit cell 10 through aportion of membrane 11 closest to the opposite electrode, e.g., negativeelectrode 32 (also referred to herein as “sink”).

[0051] The distinction between field lines and current flow can dependon a number of factors, for example, on the frequency of the appliedelectric potential and on whether electrodes 28 and 32 are electricallyinsulated. For insulated electrodes applying a DC or low frequencyalternating voltage, there is practically no current flow along thelines of the electric field. At higher frequencies, the displacementcurrents are induced in the tissue due to charging and discharging ofthe electrode insulation and the cell membranes (which act as capacitorsto a certain extent), and such currents follow the lines of the electricfield. Fields generated by non-insulated electrodes, in contrast, alwaysgenerate some form of current flow, specifically, DC or low frequencyalternating fields generate conductive current flow along the fieldlines, and high frequency alternating fields generate both conductionand displacement currents along the field lines. It should beappreciated, however, that movement of polarizable intracellularorganelles according to the present invention (as described below) isnot dependent on actual flow of current and, therefore, both insulatedand non-insulated electrodes can be used efficiently. Several advantagesof insulated electrodes are that they have lower power consumption andcause less heating of the treated regions.

[0052] According to one exemplary embodiment of the present invention,the electric fields that are used are alternating fields havingfrequencies that are in the range from about 50 KHz to about 500 KHz,and preferably from about 100 KHz to about 300 KHz. For ease ofdiscussion, these type of electric fields are also referred to below as“TC fields”, which is an abbreviation of “Tumor Curing electric fields”,since these electric fields fall into an intermediate category (betweenhigh and low frequency ranges) that have bio-effective field propertieswhile having no meaningful stimulatory and thermal effects. Thesefrequencies are sufficiently low so that the system behavior isdetermined by the system's Ohmic (conductive) properties butsufficiently high enough not to have any stimulation effect on excitabletissues. Such a system consists of two types of elements, namely, theintercellular, or extracellular fluid, or medium and the individualcells. The intercellular fluid is mostly an electrolyte with a specificresistance of about 40-100 Ohm*cm. As mentioned above, the cells arecharacterized by three elements, namely (1) a thin, highly electricresistive membrane that coats the cell; (2) internal cytoplasm that ismostly an electrolyte that contains numerous macromolecules andmicro-organelles, including the nucleus; and (3) membranes, similar intheir electric properties to the cell membrane, cover themicro-organelles.

[0053] When this type of system is subjected to the present TC fields(e.g., alternating electric fields in the frequency range of 100 KHz-300KHz) most of the lines of the electric field and currents tend away fromthe cells because of the high resistive cell membrane and therefore thelines remain in the extracellular conductive medium. In the aboverecited frequency range, the actual fraction of electric field orcurrents that penetrates the cells is a strong function of thefrequency.

[0054]FIG. 3 schematically depicts the resulting field distribution inthe system. As illustrated, the lines of force, which also depict thelines of potential current flow across the cell volume mostly inparallel with the undistorted lines of force (the main direction of theelectric field). In other words, the field inside the cells is mostlyhomogeneous. In practice, the fraction of the field or current thatpenetrates the cells is determined by the cell membrane impedance valuerelative to that of the extracellular fluid. Since the equivalentelectric circuit of the cell membrane is that of a resistor andcapacitor in parallel, the impedance is a function of the frequency. Thehigher the frequency, the lower the impedance, the larger the fractionof penetrating current and the smaller the field distortion.

[0055] As previously mentioned, when cells are subjected to relativelyweak electric fields and currents that alternate at high frequencies,such as the present TC fields having a frequency in the range of 50KHz-500 KHz, they have no effect on the non-dividing cells. While thepresent TC fields have no detectable effect on such systems, thesituation becomes different in the presence of dividing cells.

[0056] Reference is now made to FIGS. 3A-3C which schematicallyillustrate the electric current flow pattern in cell 10 during itsdivision process, under the influence of alternating fields (TC fields)in the frequency range from about 100 KHz to about 300 KHz in accordancewith one exemplary embodiment. The field lines or induced currentspenetrate cell 10 through a part of the membrane of sub-cell 16 closerto electrode 28. However, they do not exit through the cytoplasm bridge22 that connects sub-cell 16 with the newly formed yet still attachedsub-cell 14, or through a part of the membrane in the vicinity of thebridge 22. Instead, the electric field or current flow lines—that arerelatively widely separated in sub-cell 16—converge as they approachbridge 22 (also referred to as “neck” 22) and, thus, the current/fieldline density within neck 22 is increased dramatically. A “mirror image”process takes place in sub-cell 14, whereby the converging field linesin bridge 22 diverge as they approach the exit region of sub-cell 14.

[0057] It should be appreciated by persons skilled in the art thathomogeneous electric fields do not exert a force on electrically neutralobjects, i.e., objects having substantially zero net charge, althoughsuch objects can become polarized. However, under a non-uniform,converging electric field, as shown in FIGS. 3A-3C, electric forces areexerted on polarized objects, moving them in the direction of the higherdensity electric field lines. It will be appreciated that theconcentrated electric field that is present in the neck or bridge areain itself exerts strong forces on charges and natural dipoles and candisrupt structures that are associated therewith.

[0058] In the configuration of FIGS. 3A and 3B, the direction ofmovement of polarized objects is towards the higher density electricfield lines, i.e., towards the cytoplasm bridge 22 between sub-cells 14and 16. It is known in the art that all intracellular organelles, forexample, nuclei 24 and 26 of sub-cells 14 and 16, respectively, arepolarizable and, thus, such intracellular organelles are electricallyforced in the direction of the bridge 22. Since the movement is alwaysfrom lower density currents to the higher density currents, regardlessof the field polarity, the forces applied by the alternating electricfield to organelles, such as nuclei 24 and 26, are always in thedirection of bridge 22. A comprehensive description of such forces andthe resulting movement of macromolecules of intracellular organelles, aphenomenon referred to as “dielectrophoresis” is described extensivelyin literature, e.g., in C. L. Asbury & G. van den Engh, Biophys. J. 74,1024-1030, 1998, the disclosure of which is hereby incorporated byreference in its entirety.

[0059] The movement of the organelles 24 and 26 towards the bridge 22disrupts the structure of the dividing cell and, eventually, thepressure of the converging organelles on bridge membrane 22 results inthe breakage of cell membrane 11 at the vicinity of the bridge 22, asshown schematically in FIG. 3C. The ability to break membrane 11 atbridge 22 and to otherwise disrupt the cell structure and organizationcan be enhanced by applying a pulsating AC electric field, rather than asteady AC field. When a pulsating field is applied, the forces acting onorganelles 24 and 26 have a “hammering” effect, whereby pulsed forcesbeat on the intracellular organelles towards the neck 22 from bothsub-cells 14 and 16, thereby increasing the probability of breaking cellmembrane 11 in the vicinity of neck 22.

[0060] A very important element, which is very susceptible to thespecial fields that develop within the dividing cells is the microtubulespindle that plays a major role in the division process. In FIG. 4, adividing cell 10 is illustrated, at an earlier stage as compared toFIGS. 3A and 3B, under the influence of external TC fields (e.g.,alternating fields in the frequency range of about 100 KHz to about 300KHz), generally indicated as lines 100, with a corresponding spindlemechanism generally indicated at 120. The lines 120 are microtubulesthat are known to have a very strong dipole moment. This strongpolarization makes the tubules susceptible to electric fields. Theirpositive charges are located at the two centrioles while two sets ofnegative poles are at the center of the dividing cell and the other pairis at the points of attachment of the microtubules to the cell membrane,generally indicated at 130. This structure forms sets of double dipolesand therefore they are susceptible to fields of different directions. Itwill be understood that the effect of the TC fields on the dipoles doesnot depend on the formation of the bridge (neck) and thus, the dipolesare influenced by the TC fields prior to the formation of the bridge(neck).

[0061] Since the present apparatus (as will be described in greaterdetail below) utilizes insulated electrodes, the above-mentionednegative effects obtained when conductive electrodes are used, i.e., ionconcentration changes in the cells and the formation of harmful agentsby electrolysis, do not occur when the present apparatus is used. Thisis because, in general, no actual transfer of charges takes placebetween the electrodes and the medium and there is no charge flow in themedium where the currents are capacitive, i.e., are expressed only asrotation of charges, etc.

[0062] Turning now to FIG. 5, the TC fields described above that havebeen found to advantageously destroy tumor cells are generated by anelectronic apparatus 200. FIG. 5 is a simple schematic diagram of theelectronic apparatus 200 illustrating the major components thereof. Theelectronic apparatus 200 generates the desired electric signals (TCsignals) in the shape of waveforms or trains of pulses. The apparatus200 includes a generator 210 and a pair of conductive leads 220 that areattached at one end thereof to the generator 210. The opposite ends ofthe leads 220 are connected to insulated conductors 230 that areactivated by the electric signals (e.g., waveforns). The insulatedconductors 230 are also referred to hereinafter as isolects 230.Optionally and according to another exemplary embodiment, the apparatus200 includes a temperature sensor 240 and a control box 250 which areboth added to control the amplitude of the electric field generated soas not to generate excessive heating in the area that is treated.

[0063] The generator 210 generates an alternating voltage waveform atfrequencies in the range from about 50 KHz to about 500 KHz (preferablyfrom about 100 KHz to about 300 KHz) (i.e., the TC fields). The requiredvoltages are such that the electric field intensity in the tissue to betreated is in the range of about 0.1 V/cm to about 10 V/cm. To achievethis field, the actual potential difference between the two conductorsin the isolects 230 is determined by the relative impedances of thesystem components, as described below.

[0064] When the control box 250 is included, it controls the output ofthe generator 210 so that it will remain constant at the value preset bythe user or the control box 250 sets the output at the maximal valuethat does not cause excessive heating, or the control box 250 issues awarning or the like when the temperature (sensed by temperature sensor240) exceeds a preset limit.

[0065] The leads 220 are standard isolated conductors with a flexiblemetal shield, preferably grounded so that it prevents the spread of theelectric field generated by the leads 220. The isolects 230 havespecific shapes and positioning so as to generate an electric field ofthe desired configuration, direction and intensity at the target volumeand only there so as to focus the treatment.

[0066] The specifications of the apparatus 200 as a whole and itsindividual components are largely influenced by the fact that at thefrequency of the present TC fields (50 KHz-500 KHz), living systemsbehave according to their “Ohmic”, rather than their dielectricproperties. The only elements in the apparatus 200 that behavedifferently are the insulators of the isolects 230 (see FIGS. 7-9). Theisolects 200 consist of a conductor in contact with a dielectric that isin contact with the conductive tissue thus forming a capacitor.

[0067] The details of the construction of the isolects 230 is based ontheir electric behavior that can be understood from their simplifiedelectric circuit when in contact with tissue as generally illustrated inFIG. 6. In the illustrated arrangement, the electric field distributionbetween the different components is determined by their relativeelectric impedance, i.e., the fraction of the field on each component isgiven by the value of its impedance divided by the total circuitimpedance. For example, the potential drop on elementΔV_(A)=A/(A+B+C+D+E). Thus, for DC or low frequency AC, practically allthe potential drop is on the capacitor (that acts as an insulator). Forrelatively very high frequencies, the capacitor practically is a shortand therefore, practically all the field is distributed in the tissues.At the frequencies of the present TC fields (e.g., 50 KHz to 500 KHz),which are intermediate frequencies, the impedance of the capacitance ofthe capacitors is dominant and determines the field distribution.Therefore, in order to increase the effective voltage drop across thetissues (field intensity), the impedance of the capacitors is to bedecreased (i.e., increase their capacitance). This can be achieved byincreasing the effective area of the “plates” of the capacitor, decreasethe thickness of the dielectric or use a dielectric with high dielectricconstant. There a number of different materials that are suitable foruse in the intended application and have high dielectric constants. Forexample, some materials include: lithium nibate (LiNbO₃), which is aferroelectric crystal and has a number of applications in optical,pyroelectric and piezoelectric devices; yittrium iron garnet (YIG) is aferrimagnetic crystal and magneto-optical devices, e.g., opticalisolator can be realized from this material; barium titanate (BaTiO₃) isa ferromagnetic crystal with a large electro-optic effect; potassiumtantalate (kTaO₃) which is a dielectric crystal (ferroelectric at lowtemperature) and has very low microwave loss and tunability ofdielectric constant at low temperature; and lithium tantalate (LiTaO₃)which is a ferroelectric crystal with similar properties as lithiumniobate and has utility in electro-optical, pyroelectric andpiezoelectric devices. It will be understood that the aforementionedexemplary materials can be used in combination with the present devicewhere it is desired to use a material having a high dielectric constant.

[0068] In order to optimize the field distribution, the isolects 230 areconfigured differently depending upon the application in which theisolects 230 are to be used. There are two principle modes for applyingthe present electric fields (TC fields). First, the TC fields can beapplied by external isolects and second, the TC fields can be applied byinternal isolects.

[0069] Electric fields (TC fields) that are applied by external isolectscan be of a local type or widely distributed type. The first typeincludes, for example, the treatment of skin tumors and treatment oflesions close to the skin surface. FIG. 7 illustrates an exemplaryembodiment where the isolects 230 are incorporated in a skin patch 300.The skin patch 300 can be a self-adhesive flexible patch with one ormore pairs of isolects 230. The patch 300 includes internal insulation310 (formed of a dielectric material) and the external insulation 260and is applied to skin surface 301 that contains a tumor 303 either onthe skin surface 301 or slightly below the skin surface 301. Tissue isgenerally indicated at 305. To prevent the potential drop across theinternal insulation 310 to dominate the system, the internal insulation310 must have a relatively high capacity. This can be achieved by alarge surface area; however, this may not be desired as it will resultin the spread of the field over a large area (e.g., an area larger thanrequired to treat the tumor). Alternatively, the internal insulation 310can be made very thin and/or the internal insulation 310 can be of ahigh dielectric constant. As the skin resistance between the electrodes(labeled as A and E in FIG. 6) is normally significantly higher thanthat of the tissue (labeled as C in FIG. 6) underneath it (1-10 KΩ vs.0.1-1 KΩ), most of the potential drop beyond the isolects occurs there.To accommodate for these impedances (Z), the characteristics of theinternal insulation 310 (labeled as B and D in FIG. 6) should be suchthat they have impedance preferably under 100 KΩ at the frequencies ofthe present TC fields (e.g., 50 KHz to 500 KHz). For example, if it isdesired for the impedance to be about 10K Ohms, such that over 1% of theapplied voltage falls on the tissues, for isolects with a surface areaof 10 mm², at frequencies of 200 KHz, the capacity should be on theorder of 10⁻¹⁰ F, which means that using standard insulations with adielectric constant of 2-3, the thickness of the insulating layer 310should be about 50-100 microns. An internal field 10 times strongerwould be obtained with insulators with a dielectric constant of about20-50.

[0070] Since the insulating layer can be very vulnerable, etc., theinsulation can be replaced by very high dielectric constant insulatingmaterials, such as titanium dioxide (e.g., rutil), the dielectricconstant can reach values of about 200. One must also consider anotherfactor that effects the effective capacity of the isolects 230, namelythe presence of air between the isolects 230 and the skin. Suchpresence, which is not easy to prevent, introduces a layer of aninsulator with a dielectric constant of 1.0, a factor that significantlylowers the effective capacity of the isolects 230 and neutralizes theadvantages of the titanium dioxide (routil), etc. To overcome thisproblem, the isolects 230 can be shaped so as to conform with the bodystructure and/or (2) an intervening filler 270 (as illustrated in FIG.1C), such as a gel, that has high conductance and a dielectric constant,can be added to the structure. The shaping can be pre-structured (seeFIG. 10A) or the system can be made sufficiently flexible so thatshaping of the isolects 230 is readily achievable. The gel can becontained in place by having an elevated rim as depicted in FIG. 10C.The gel can be made of gelatins, agar, etc., and can have saltsdissolved in it to increase its conductivity. FIGS. 10A-10C illustratevarious exemplary configurations for the isolects 230. The exactthickness of the gel is not important so long as it is of sufficientthickness that the gel layer does not dry out during the treatment. Inone exemplary embodiment, the thickness of the gel is about 0.5 mm toabout 2 mm.

[0071] In order to achieve the desirable features of the isolects 230,the dielectric coating of each should be very thin, for example frombetween 1-50 microns. Since the coating is so thin, the isolects 230 caneasily be damaged mechanically. This problem can be overcome by adding aprotective feature to the isolect's structure so as to provide desiredprotection from such damage. For example, the isolect 230 can be coated,for example, with a relatively loose net 340 that prevents access to thesurface but has only a minor effect on the effective surface area of theisolect 230 (i.e., the capacity of the isolects 230 (cross sectionpresented in FIG. 12B). The loose net 340 does not effect the capacityand ensures good contact with the skin, etc. The loose net 340 can beformed of a number of different materials; however, in one exemplaryembodiment, the net 340 is formed of nylon, polyester, cotton, etc.Alternatively, a very thin conductive coating 350 can be applied to thedielectric portion (insulating layer) of the isolect 230. One exemplaryconductive coating is formed of a metal and more particularly of gold.The thickness of the coating 350 depends upon the particular applicationand also on the type of material used to form the coating 350; however,when gold is used, the coating has a thickness from about 0.1 micron toabout 0.1 mm. Furthermore, the rim illustrated in FIG. 10 can alsoprovide some mechanical protection.

[0072] However, the capacity is not the only factor to be considered.The following two factors also influence how the isolects 230 areconstructed. The dielectric strength of the internal insulating layer310 and the dielectric losses that occur when it is subjected to the TCfield, i.e., the amount of heat generated. The dielectric strength ofthe internal insulation 310 determines at what field intensity theinsulation will be “shorted” and cease to act as an intact insulation.Typically, insulators, such as plastics, have dielectric strength valuesof about 100V per micron or more. As a high dielectric constant reducesthe field within the internal insulator 310, a combination of a highdielectric constant and a high dielectric strength gives a significantadvantage. This can be achieved by using a single material that has thedesired properties or it can be achieved by a double layer with thecorrect parameters and thickness. In addition, to further decreasing thepossibility that the insulating layer 310 will fail, all sharp edges ofthe insulating layer 310 should be eliminated as by rounding thecorners, etc., as illustrated in FIG. 10D using conventional techniques.

[0073]FIGS. 8 and 9 illustrate a second type of treatment using theisolects 230, namely electric field generation by internal isolects 230.A body to which the isolects 230 are implanted is generally indicated at311 and includes a skin surface 313 and a tumor 315. In this embodiment,the isolects 230 can have the shape of plates, wires or other shapesthat can be inserted subcutaneously or a deeper location within the body311 so as to generate an appropriate field at the target area (tumor315).

[0074] It will also be appreciated that the mode of isolects applicationis not restricted to the above descriptions. In the case of tumors ininternal organs, for example, liver, lung, etc., the distance betweeneach member of the pair of isolects 230 can be large. The pairs can evenby positioned opposite sides of a torso 410, as illustrated in FIG. 11.The arrangement of the isolects 230 in FIG. 11 is particularly usefulfor treating a tumor 415 associated with lung cancer. In thisembodiment, the electric fields (TC fields) spread in a wide fraction ofthe body.

[0075] In order to avoid overheating of the treated tissues, a selectionof materials and field parameters is needed. The isolects insulatingmaterial should have minimal dielectric losses at the frequency rangesto be used during the treatment process. This factor can be taken intoconsideration when choosing the particular frequencies for thetreatment. The direct heating of the tissues will most likely bedominated by the heating due to current flow (given by the I*R product).

[0076] The effectiveness of the treatment can be enhanced by anarrangement of isolects 230 that focuses the field at the desired targetwhile leaving other sensitive areas in low field density (i.e.,protected areas). The proper placement of the isolects 230 over the bodycan be maintained using any number of different techniques, includingusing a suitable piece of clothing that keeps the isolects at theappropriate positions. FIG. 13 illustrates such an arrangement in whichan area labeled as “P” represents a protected area. The lines of fieldforce do not penetrate this protected area and the field there is muchsmaller than near the isolects 230 where target areas can be located andtreated well. In contrast, the field intensity near the four poles isvery high.

[0077] The following Example serves to illustrate an exemplaryapplication of the present apparatus and application of TC fields;however, this Example is not limiting and does not limit the scope ofthe present invention in any way.

EXAMPLE

[0078] To demonstrate the effectiveness of electric fields having theabove described properties (e.g., frequencies between 50 KHz and 500KHz) in destroying tumor cells, the electric fields were applied totreat mice with malignant melanoma tumors. Two pairs of isolects 230were positioned over a corresponding pair of malignant melanomas. Onlyone pair was connected to the generator 210 and 200 KHz alternatingelectric fields (TC fields) were applied to the tumor for a period of 6days. One melanoma tumor was not treated so as to permit a comparisonbetween the treated tumor and the non-treated tumor. After treatment for6 days, the pigmented melanoma tumor remained clearly visible in thenon-treated side of the mouse, while, in contrast, no tumor is seen onthe treated side of the mouse. The only areas that were visiblediscernable on the skin were the marks that represented the points ofinsertion of the isolects 230. The fact that the tumor was eliminated atthe treated side was further demonstrated by cutting and inversing theskin so that its inside face was exposed. Such a procedure indicatedthat the tumor has been substantially, if not completely, eliminated onthe treated side of the mouse. The success of the treatment was alsofurther verified by pathhistological examination.

[0079] The present inventor has thus uncovered that electric fieldshaving particular properties can be used to destroy dividing cells ortumors when the electric fields are applied to using an electronicdevice. More specifically, these electric fields fall into a specialintermediate category, namely bio-effective fields that have nomeaningful stimulatory and no thermal effects, and therefore overcomethe disadvantages that were associated with the application ofconventional electric fields to a body. It will also be appreciated thatthe present apparatus can further include a device for rotating the TCfield relative to the living tissue. For example and according to oneembodiment, the alternating electric potential applies to the tissuebeing treated is rotated relative to the tissue using conventionaldevices, such as a mechanical device that upon activation, rotatesvarious components of the present system.

[0080] While the invention has been particularly shown and describedwith reference to preferred embodiments thereof, it will be understoodby those skilled in the art that various changes in form and details canbe made without departing from the spirit and scope of the invention.

What is claimed is:
 1. An apparatus for selectively destroying dividingcells in living tissue, the dividing cells having polarizable or polarintracellular members, the apparatus comprising: a first insulatedelectrode having a first conductor; a second insulated electrode havinga second conductor; and an electric field source for applying analternating electric potential across the first and second conductors,wherein passage of the electric field through the dividing cells in lateanaphase or telophase transforms the electric field into anon-homogenous electric field that produces an increased densityelectric field in a region of a cleavage furrow of the dividing cells,the non-homogeneous electric field produced within the dividing cellsbeing of sufficient intensity to move the polarizable intracellularmembers toward the cleavage.
 2. The apparatus of claim 1, wherein theelectric field is of sufficient frequency so that the non-homogeneouselectric field produced in the dividing cells defines electric fieldlines which generally converge at a region of the cleavage furrow,thereby defining the increased density electric field, resulting indestruction of the dividing cells as a result of the polarizableintracellular members movement toward the furrow.
 3. The apparatus ofclaim 1, further including: a first conductive lead operativelyconnecting the first electrode to the electric field source; and asecond conductive lead operatively connecting the second electrode tothe electric field source.
 4. The apparatus of claim 1, wherein thefirst electrode includes a first dielectric member that is in contactwith the first conductor, the first dielectric member for placementagainst the living tissue to form a capacitor.
 5. The apparatus of claim4, wherein the second electrode includes a second dielectric member thatis in contact with the second conductor, the second dielectric memberfor placement against the living tissue to form a capacitor.
 6. Theapparatus of claim 5, wherein each of the first and second dielectricmembers is formed of a layer of titanium dioxide.
 7. The apparatus ofclaim 5, wherein each of the first and second dielectric memberscomprises a dielectric coating having a thickness between about 5microns to about 50 microns.
 8. The apparatus of claim 7, furtherincluding: a loose net disposed around the dielectric coating forrestricting access to a surface of the dielectric coating while onlyhaving a minimal effect on a surface area of the dielectric coating. 9.The apparatus of claim 7, further including: a thin conducting coatingdisposed on the dielectric coating for contacting the tissue.
 10. Theapparatus of claim 9, wherein the conducting coating is formed of gold.11. The apparatus of claim 1, wherein the alternating electric potentialhas a frequency of between about 50 KHz to about 500 KHz.
 12. Theapparatus of claim 1, wherein the alternating electric potential has afrequency of between about 100 KHz to about 300 KHz.
 13. The apparatusof claim 1, wherein the electric field is a substantially uniformelectric field prior to passing through the dividing cells.
 14. Theapparatus of claim 1, wherein the electric field source comprises agenerator that generates an alternating voltage waveform at frequenciesbetween about 50 KHz to about 500 KHz.
 15. The apparatus of claim 14,wherein each of the first and second electrodes are activated by thealternating voltage waveform.
 16. The apparatus of claim 14, wherein thevoltage waveform is selected so that an electric field intensity intissue to be treated is between about 0.1 V/cm to about 10.0 V/cm. 17.The apparatus of claim 1, further including: a control box operativelyconnected to the electric field source; and a temperature sensor coupledto the control box, wherein the control box and the temperature sensorcontrol the amplitude of the electric field generated so that excessiveheating in a treated area is prevented.
 18. The apparatus of claim 5,wherein at least one of the first and second electrodes includes anintervening filler disposed on the respective dielectric member thereof,the intervening filler being formed of a material that has highconductance and a high dielectric constant.
 19. The apparatus of claim 18, wherein the intervening filler comprises a gel formed of at least onematerial selected from the group consisting of gelatins and agar. 20.The apparatus of claim 19, wherein the gel includes salt dissolvedtherein to increase the conductivity of the gel.
 21. The apparatus ofclaim 18, wherein the intervening filler is contained within thedielectric member by a rim formed as part of the dielectric member. 22.The apparatus of claim 1, wherein the first and second electrodes areinternal members that are inserted within the body.
 23. The apparatus ofclaim 22, wherein the first and second electrodes are incorporated intoa structure that is inserted subcutaneously within the body.
 24. Theapparatus of claim 1, wherein the first and second electrodes areconfigured for placement on opposite sides of a torso with the dividingcells being associated with a tumor that is formed within the body at alocation between the first and second electrodes.
 25. A skin patch forselectively destroying dividing cells that are in a localized area ofliving tissue, the dividing cells having polarizable or polarintracellular members, the skin patch including: a skin patch body forplacement on the living tissue over the localized area of dividingcells, the skin patch body comprising: a first insulated electrodehaving a first conductor; a second insulated electrode having a secondconductor; and an electric field source for applying an alternatingelectric potential across the first and second conductors, whereinpassage of the electric field through the dividing cells in lateanaphase or telophase transforms the electric field into anon-homogenous electric field that produces an increased densityelectric field in a region of a cleavage furrow of the dividing cells,the non-homogeneous electric field produced within the dividing cellsbeing of sufficient intensity to move the polarizable intracellularmembers toward the cleavage furrow.
 26. The skin patch of claim 25,wherein the electric field is of sufficient frequency so that thenon-homogeneous electric field produced in the dividing cells defineselectric field lines which generally converge at a region of thecleavage furrow, thereby defining the increased density electric field,resulting in destruction of the dividing cells as a result of thepolarizable intracellular members movement toward the furrow.
 27. Theskin patch of claim 25, wherein the alternating electric potential has afrequency of between about 50 KHz to about 500 KHz.
 28. The skin patchof claim 25, wherein the alternating electric potential has a frequencyof between about 100 KHz to about 300 KHz.
 29. The skin patch of claim25, wherein the electric field is a substantially uniform electric fieldprior to passing through the dividing cells.
 30. The skin patch of claim25, wherein the electric field source comprises a generator thatgenerates an alternating voltage waveform at frequencies between about50 KHz to about 500 KHz.
 31. The skin patch of claim 29, wherein each ofthe first and second electrodes are activated by the alternating voltagewaveform.
 32. The skin patch of claim 29, wherein the voltage waveformis selected so that an electric field intensity in tissue to be treatedis between about 0.1 V/cm to about 10.0 V/cm.
 33. The skin patch ofclaim 25, further including: a control box operatively connected to theelectric field source; and a temperature sensor coupled to the controlbox, wherein the control box and the temperature sensor control theamplitude of the electric field generated so that excessive heating in atreated area is prevented.
 34. The skin patch of claim 25, furthercomprising: at least one additional insulated electrode having acorresponding conductor that is coupled to the electric field source.35. The skin patch of claim 34, wherein all of the insulated electrodesare arranged to focus the electric field at a target within thelocalized area of the living tissue while also forming a protected areawhich has a low electric field density.
 36. A method for selectivelydestroying dividing cells in living tissue, the dividing cells havingpolarizable intracellular members, the method comprising the steps of:providing an apparatus having: a first insulated electrode; a secondinsulated electrode; and an electric field source for applying analternating electric potential across the first and second conductors;positioning the first and second insulated electrodes in relation to theliving tissue; and subjecting the living tissue to the alternatingelectric field, wherein passage of the electric field through thedividing cells in late anaphase or telophase transforms the electricfield into a non-homogeneous electric field that produces an increaseddensity electric field in a region of cleavage furrow of the dividingcells, the non-homogeneous electric field being of sufficient intensityto move the intracellular members toward the cleavage furrow until theintracellular members disrupt the cleavage furrow.
 37. The method ofclaim 36, wherein the electric field is of sufficient frequency so thatthe non-homogeneous electric field produced in the dividing cellsdefines electric field lines which generally converge at a region of thecleavage furrow, thereby defining the increased density electric field,resulting in destruction of the dividing cells as a result of thepolarizable intracellular members movement toward the furrow.
 38. Themethod of claim 36, wherein positioning the first and second electrodescomprises: positioning dielectric members of each conductor against theliving tissue to form a capacitor.
 39. The method of claim 36, whereinsubjecting the living tissue to the alternating electric field comprisesapplying an alternating electric potential having a frequency of betweenabout 50 KHz to about 500 KHz.
 40. The method of claim 36, wherein thedividing cells comprise a first sub-cell and a second sub-cell with thecleavage furrow connecting the two in late anaphase or telophase. 41.The method of claim 36, further comprising the step of: rotating theelectric field source relative to the living tissue.
 42. The method ofclaim 36, wherein movement of the intracellular members toward thecleavage furrow increases pressure being exerted on the cleavage furrow,the increased pressure causing the region of the cleavage furrow toexpand resulting in the cleavage furrow breaking apart and causingdestruction of the dividing cells.
 43. An apparatus for selectivelydestroying dividing cells that are in a localized area of living tissue,the dividing cells having polarizable intracellular members, theapparatus comprising: at least two insulated electrodes with eachelectrode having an associated conductor and a dielectric material forplacement against living tissue; and an electric field source forapplying an alternating electric potential across the conductors suchthat a resulting electric field in the dividing cells is transformedinto a non-homogenous electric field that produces an increased densityelectric field in a region of the dividing cells, the non-homogenouselectric field being of sufficient intensity to cause the intracellularmembers to be drawn to the region where the electric field has increaseddensity to cause a pressure increase in this region which causes astructural breakdown of the dividing cells.